The Special Issue of International Journal of Molecular Sciences on the topic "Making Bioactive Peptides Druggable: Challenges and Prospects" is intended to be an up-to-date collection of works, either original or literature reviews, which highlight the current challenges, approaches, and prospects towards the improvement of peptide pharmacokinetics.

The growing relevance of peptides in many areas of industrial and academic R&D is undeniable. Peptides have been explored in the most diverse fields, from molecular biology to materials science, from synthetic chemistry to computational and structural biology, from food science to biotechnology, from early drug discovery to clinics. The huge potential of bioactive peptides, especially, but not exclusively, for therapeutic applications, has been a major driving force for the development of robust chemical methods for peptide synthesis in the second half of the 20th century, with Merrifield’s solid-phase peptide synthesis (SPPS) emerging in the 1960s as the most revolutionary achievement. At present, researchers have easy access to a panoply of building blocks, as well as chemical and synthetic biology approaches to produce the most diverse peptides and peptidomimetics. Yet, two decades have passed in the 21st century and there is still one major obstacle to be overcome if the clinical translation of bioactive peptides is to become a trivial matter: making bioactive peptides druggable. Abolishing the well-known limitations of bioactive peptides as therapeutics, mostly due to their poor pharmacokinetics, is currently a top-priority for peptide scientists worldwide.